Pattern of uveitis in a referral ophthalmology center in Northeastern Thailand

Purpose To report the characteristics and epidemiology of uveitis in a university-based referral center in northeastern Thailand and review the uveitis patterns present in various regions worldwide. Methods A retrospective review of all medical records for new patients visiting the uveitis clinic at Srinagarind hospital, Khon Kaen University, between August 2016 and June 2021, was conducted. Results A total of 522 uveitis patients were included in this study. Disease etiologies were categorized as non-infectious 35.8% (187/522), infectious 32.8% (171/522), and undetermined cause 31.4% (164/522). Specific diagnoses were established in 68.6% of cases. Vogt-Koyanagi-Harada (VKH) (14.2%) was identified as the most common specific diagnosis, and tuberculosis (6.7%) ranked highest among infectious causes. Conclusions Although non-infectious uveitis is observed predominantly in this region, the proportion of infectious uveitis is relatively more common than in developed countries. We have found no cause for one-third of our patients despite the utilization of PCR and serology for diagnostic purposes.


Introduction
Uveitis comprises a group of ocular disorders characterized by inflammation within the eye, leading to a significant visual impairment, accounting for 5-10% of causes of legal blindness [1,2].The etiology of uveitis varies globally due to factors such as geographic location and demographic differences among populations.Epidemiological studies on uveitis in Thailand have, to date, primarily focused on the central, northern and southern region [3][4][5][6][7][8].This study aims to report the patterns of uveitis at the Department of Ophthalmology, Srinagarind Hospital, a referral center for ophthalmology in the northeastern part of Thailand.

Pattern of uveitis in a referral ophthalmology center in Northeastern Thailand
Trakanta Wannapanich 1 , Waraporn Chuenchaem 1 , Patanaree Luanratanakorn 1 and Wipada Laovirojjanakul 1* involving slit-lamp biomicroscopy, applanation tonometry, and dilated fundus examination, was conducted for all patients.Additional investigations, such as fundus fluorescein angiography, indocyanine green angiography, and optical coherence tomography, were determined by a uveitis specialist.Specific diagnoses were confirmed or strongly suspected based on clinical history, ocular findings, laboratory results, and ancillary tests, with definite diagnoses relying on the best available evidence during the study period.
Tests for infectious causes included Venereal Disease Research Laboratory (VDRL), Treponema pallidum hemagglutination (TPHA) test, interferon gamma releasing assay (IGRA; QuantiFERON-TB Gold test), polymerase chain reaction (PCR) for Mycobacterium tuberculosis, toxoplasma antibody testing, toxocara antibody testing, serum enzyme-linked immunosorbent assay (ELISA) for specific parasites (Gnathostoma spp., Angiostrongylus spp.), human immunodeficiency virus (HIV) antibody test, viral antibody testing, PCR for herpes viruses, microbiological cultures, and any evidence of ongoing systemic infection at the time of uveitis onset.The diagnosis of ocular toxocariasis primarily relied on clinical findings such as retinal granuloma, tractional retinal detachment, vitreous haze and, when available, correlation with serological tests.The diagnosis of ocular parasitic infections also included the identification of parasites in any part of the eye, such as Gnathostoma spp., Angiostrongylus spp., and cysticercosis.Investigations for non-infectious etiologies encompassed antinuclear activity (ANA), rheumatoid factor, anti-ds-DNA, anti-neutrophil cytoplasmic antibodies (ANCA), and human leukocyte antigen typing (HLA-B27).When necessary, we performed anterior chamber paracentesis to obtain aqueous fluid specimens.Additionally, vitreous samples were collected through diagnostic pars plana vitrectomy.The choice of ancillary tests was determined case-by-case based on clinical suspicions.
To assess visual impairment, low vision was defined as best corrected visual acuity (BCVA) less than 6/18 using Snellen chart but equal to or better than 3/60 in the better eye.Blindness was defined as BCVA less than 3/60 in the better eye [10].Complication assessment included the identification of glaucoma when intraocular pressure (IOP) exceeding 21 mmHg with further evidences of glaucomatous optic neuropathy.Ocular hypertension was defined as a transient IOP elevation greater than 21 mmHg without the need for IOP-lowering drugs.Ocular hypotony was characterized by an IOP lower than 6 mmHg.Secondary cataract was considered when patients developed nuclear sclerosis and/or posterior subcapsular cataracts to a greater degree than expected for their age or exhibited asymmetrical cataracts with greater severity in the affected eye for unilateral uveitis patients.Data recording and descriptive statistical analysis were performed using Microsoft Excel (version 16.16.4,Microsoft, Raymond, WA).
The diagnoses of all patients are detailed in Table 2. Disease etiologies were categorized as non-infectious 35.8% (187/522), infectious 32.8% (171/522), and undetermined cause 31.4% (164/522).Vogt-Koyanagi-Harada (14.2%) was the most frequent cause of uveitis among the non-infectious group, followed by Behcet's disease (9.0%) and HLA-B27 associated anterior uveitis (4.2%).There were three cases diagnosed with intraocular lymphoma, with two cases presenting with unilateral posterior uveitis and one case presenting with bilateral panuveitis.Coat's disease was included in the uveitis clinic because the patient was consulted due to retinal infiltration suspected as posterior uveitis.Therefore, Coat's disease may be categorized under the pediatric masqueraders group.Among the infectious group, ocular tuberculosis (6.7%), herpetic anterior uveitis (5.2%) and ocular toxoplasmosis (5.0%) were the most common pathogens (Table 2).

Visual assessment
Out of 271 patients with bilateral uveitis, blindness occurred in 27 patients (10.0%), mostly caused by VKH (9 patients).Low vision was recorded in 69 patients (25.5%), with Behcet's disease (12 patients) being the leading cause, followed by VKH (9 patients).Unilateral uveitis led to blindness in the affected eye in 62 out of 251 patients (24.7%) with the majority caused by acute retinal necrosis (9 patients) and herpetic anterior uveitis (7 patients).
Intraocular tuberculosis (IOTB), diagnosed based on the classification mentioned earlier [24], accounted for the largest number of patients in the infectious group, frequently manifesting with chorioretinitis (13 patients) and retinal vasculitis (12 patients).The finding aligns with studies by Sukavatcharin et al [7], Rajan et al [25], and Nguyen et al [23], which reported tuberculosis diagnoses in 8.6%, 8.7, and 9.0% of uveitis patients, respectively.Additional studies has highlighted tuberculosis as the most prevalent infectious pathogens, constituting 32% in Myanmar [20] and 18.5% in India [26].Conversely, studies in other regions of Thailand reported herpetic uveitis, toxoplasmosis, or CMV uveitis as the most prevalent infectious etiologies [3][4][5][6][7][8].In anterior uveitis patients in this study, viral infection emerged as the most common cause of inflammation, consistent with studies from central Thailand [6], Vietnam [23], Malaysia [25], and Ethiopia [27], rather than HLA-B27 or ankylosing spondylitis, which were frequently more reported in most Asian countries [3,5,7,18,21,26,28], except Myanmar which reported tuberculosis [20].Toxoplasmosis was a common specific diagnosis in the posterior  uveitis group, similar to reports from India [29], North Africa [12], Iraq [16], and Ethiopia [27].Risk factors associated with infectious uveitis cases depend on the infectious etiologies involved.Given that Thailand is an endemic area for tuberculosis infection, it is considered one of the risk factors for IOTB, along with documented exposure to tuberculosis and clinical evidence of extraocular tuberculosis manifestations.Additionally, most patients with CMV retinitis were either known cases of HIV infection or were immunocompromised.Patients with poor personal and community hygiene, or those who consume contaminated/raw food products, are at risk for ocular parasitic infections.Unlike studies conducted in other regions of Thailand, this study found panuveitis to be the most common anatomical location.Regarding etiology, infectious causes accounted for 32.8%, with IOTB being the most common specific diagnosis at 6.7%.Compared to other regions, northeastern Thailand showed differences in both clinical presentation and etiology, with a higher prevalence of panuveitis and TB-associated uveitis.Further details regarding studies conducted in other regions of Thailand are listed in Table 4.
It is noteworthy that nearly one-third (31.4%) of the patients in this study have unspecified diagnoses of their intraocular inflammation.The prevalence of this subgroup of patients varies significantly among studies, ranging from as low as 13% in a Thai study [3] to as high as 86.1% in a report from Sweden [30].Recent research indicates that in the era of PCR, an increasing number of uveitis cases with undetermined etiology are obtaining specific diagnoses through aqueous or vitreous specimen samplings, particularly in cases of infectious etiologies such as viral and toxoplasma infection [31,32].Despite a report of low diagnostic utility in one study [33], these positive outcomes have the potential to alter treatment regimens, leading to treatment success [31,32].We believe that the availability of PCR and deep sequencing    technique will decrease the proportion of patients with idiopathic uveitis.The most frequent ocular complication in this study was glaucoma, occurring in approximately one-fifth of the patients, a figure comparable to a study from central Thailand [8].Another Thai study reported cataract as the most common uveitis sequelae [6].In our clinical practice, cataract grading is subjectively determined by each ophthalmologist and may vary between visits.Therefore, we acknowledge that cataracts may be underestimated as a complication of uveitis.
However, the study has limitations, notably the potential under-recording of CMV retinitis patients as only 21 HIV-infected patients were included.Additionally, cataracts might be underreported as a uveitis complication due to the cross-sectional study design.Long-term follow-up is suggested to accurately determine the incidence of secondary cataracts.Finally, given that our hospital serves as the tertiary uveitis referral center in northeastern Thailand, the majority of our patients were referred from other hospitals.Consequently, the epidemiological data presented in this study may not be directly comparable to findings from smaller-scale healthcare institutions or different geographical regions.
In conclusion, panuveitis predominated among patients in this study.Tuberculosis was the most frequent infectious cause, while VKH was the most common etiology among non-infectious uveitis patients.Glaucoma was a common association with uveitis in this study.Although non-infectious uveitis is observed predominantly in this region, the proportion of infectious uveitis is relatively more common than in developed countries.
Demographic and clinical characteristics by anatomical involvement

Table 2
Patient characteristics listed by anatomical site and definite diagnosis

Table 3
Complications of uveitis found in this study

Table 4
Pattern of uveitis in Thailand